四氢原小檗碱对吗啡成瘾大鼠脑中腹侧被盖区神经胶质纤维酸性蛋白和酪氨酸羟化酶含量的影响

目的　研究吗啡依赖对大鼠中脑腹侧被盖区(VTA)神经元功能变化以及四氢原小檗碱 (THPB)的干预作用。方法　大鼠ip递增剂量的吗啡 10d建立吗啡依赖模型 ,d 11起分别ipTHPB 30mg·kg- 1或等体积生理盐水 (NS) ,每天 2次 ,治疗 12d或 30d。取脑 ,冰冻切片 ,用ABC法测VTA等脑区神经胶质纤维酸性蛋白 (GFAP)和酪氨酸羟化酶 (TH)的免疫组织化学反应 ,测定其阳性神经元的平均吸光度值表示其含量。结果　吗啡成瘾大鼠VTA中GFAP和TH免疫阳性神经元含量持续高于正常对照组 (P <0 .0 5 ) ;THPB治疗 12d或 30d显著降低GFAP和TH免疫阳性神经元含量的增高 ,与正常对照组比无显著性差异。结论　吗啡成瘾造成大鼠脑VTA“特异性损伤” ,THPB可逆转此损伤 ,对吗啡成瘾大鼠脑有保护作用 ,提示其有可能用于阿片类成瘾的防治。

Effect of tetrahydroprotoberberines on contents of glial fibrillary acidic protein and tyrosine hydroxylase in ventral tegmental area of morphine dependent rats

AIM To determine the effects of tetrahydroprotoberberines (THPB) on functions of neurons in the ventral tegmental area (VTA) of morphine-dependent rats. METHODS Rats received daily increasing dose of morphine for 10 d (5, 10, 15, 20, 25, 30, 35, 40, 45, 50 mg·kg^-1, respectively, ip, twice a day) to establish morphine dependence, then were given normal saline (NS) or THPB 30 mg·kg^-1, ip, twice daily for 12 d or 30 d. Control group received ip NS all the time. The levels of glial fibrillary acidic protein(GFAP) and tyrosine hydroxylase(TH) were determined as immunohistochemical intensity by ABC method and image analysis. RESULTS Levels of GFAP and TH in the VTA region of morphine-dependent rats were higher than those of control group (P<0.05)，while groups treated with THPB were similar to those of control group (P>0.05). CONCLUSION Higher levels of GFAP and TH indicate that morphine- dependence induces impairment of dopaminergic functions in the VTA region. THPB treatment can reverse the damage, which suggest that THPB be benefit for clinical use to prevent heroin relapse.